AB0601 FACTORS ASSOCIATED WITH THROMBOSIS IN BEHÇET SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: G. Guzelant Ozkose, B. Yurttas, M. C. Ar, S. N. Esatoglu, V. Hamuryudan, H. Yazici, G. Hatemi
Journal: Annals of the Rheumatic Diseases (2022)

Background Behçet syndrome (BS) is a unique vasculitis that can affect arteries and veins of all sizes. Thrombosis is an important component of vascular involvement in BS. Although several studies were conducted to highlight the mechanism of thromboinflammation in BS, it is still not fully understood. Objectives We performed a systematic review and meta-analysis of studies investigating thrombotic, fibrinolytic, and endothelial factors in BS. Methods We searched PubMed and EMBASE with the keyword “Behcet*” in four languages (English, German, French and Turkish) from their inception up to April 2020. Titles and/or abstracts of all studies were screened independently by two reviewers (GGO and BY) and conflicts were solved by a third reviewer (GH). Studies comparing BS patients with and without thrombosis and studies comparing BS patients with thrombosis and patients with thrombosis due to other causes were analyzed separately. The pooled odds ratios (OR) with 95%CI were calculated for binary outcomes and standardized mean differences (MD) were calculated for continuous outcomes using RevMan 5.3. We categorized the factors into 4 groups based on acting mechanism 1- those that decrease anticoagulant activity 2- those that increase procoagulant activity 3- those that decrease the activity of fibrinolytic system 4- pathogenetic/endothelial factors. Results Of 15548 articles, 15157 were excluded due to duplication and inappropriate study design after reviewing titles and abstracts. Full text review of the remaining 391 articles yielded 103 papers meeting our predetermined inclusion criteria. Factors significantly associated with BS thrombosis compared to BS without thrombosis were high frequency of factor V Leiden mutation (15 studies, OR 2.55, 95%CI 1.66-3.93), high homocysteine level (14 studies, MD: 4.27, 95%CI 2.31-6.22), high protein C level (5 studies, SMD: 0.80, 95%CI 0.15-1.45) and high alpha1-antitrypsin level (1 study, MD: 3.00, 95%CI 0.15-5.85) in Group 1; high factor 8 level (4 studies, MD: 17.17, 95%CI 7.79-6.55), high thrombin level (1 study, MD: 35.90, 95%CI 12.40-59.40), high neutrophil/lymphocyte ratio (2 studies, MD: 1.37, 95%CI 0.24-2.50) and high platelet/neutrophil complex level (1 study, MD: 10.50, 95%CI 0.76-20.24) in Group 2; high TAFI activity (1 study, MD: 28, 95%CI 4.12-51.88) in Group 3; high VEGF level (2 studies, SMD: 1.63, 95%CI 0.21-3.05), high CEC concentration (2 studies, SMD: 1.00, 95%CI 0.22-1.77), high MCP-1 level (1 study, MD: 74.16, 95%CI 61.29-87.03), high anti-C1q level (1 study, MD: 9.11, 95%CI 0.51-17.71), high platelet microaggregate formation (1 study, MD: 75.00, 95%CI 7.62-142.38), high frequency of P-selectin glycoprotein ligand 1 gen polymorphism (heterozygous (AB+AC+BC)) (1 study, OR: 1.88, 95%CI 1.07-3.31), high ADMA level (1 study, MD: 0.16, 95%CI 0.08-0.24), high sICAM-1 level (1 study, MD: 59.30, 95%CI 3.35-115.25) and low brachial artery flow-mediated (endotelium-dependant) dilatation (1 study, MD: -3.22, 95%CI -5.18--1.26) in Group 4. Factors that were associated with BS thrombosis compared to thrombosis due to other causes including JAK-2 mutation, circulating endothelial cells, activated protein C resistance, tPA, and PAI were assessed in 1 study each. Among these, tPA levels (MD: -6.00, 95%CI -10.99--1.01), APCR (OR: 0.09, 95%CI 0.01-0.73) and JAK-2 mutations (OR: 0.01, 95%CI 0.00-0.06) were significantly less in patients with BS thrombosis compared to patients with thrombosis due to other causes. Conclusion Several factors were identified that may potentially be associated with thrombosis in BS. However, the cut-offs used for defining the normal level for these factors, time of blood collection (during acute or chronic stage of thrombosis, use of anticoagulants) and the type of thrombosis (arterial, venous, or cerebral sinus) were not uniform across the studies. Studies investigating these factors together, in a large number of patients, and together with appropriate controls are needed to confirm these results. Disclosure of Interests None declared